Antimicrobial strategies in the past have focused on reducing plaque overall and inhibiting its reformation to prevent caries. However, it is now known that the development of carious lesions is an intricate process involving microbial specificity (the mutans streptococci) and a multitude of dietary and host-derived factors. The 'ecological plaque hypothesis' embraces these interplaying components by proposing that one or more of these factors triggers a shift in proportions of plaque organisms thereby creating a more cariogenic flora. Therefore, a more rational approach in caries prevention would focus on inhibiting these deleterious shifts in microbial communities where the mutans streptococci become dominant. Our central hypothesis that exposure of the mutans streptococci to combinations of a metal ion (copper-Cu++) and chlorhexidine (CHX), or pyrophosphate (PPi) with sodium dodecyl sulfate (SDS) and fluoride (F), will affect the ability of these organisms to colonize teeth. The Specific Aims of this proposal are: 1. Assess the antimicrobial activity of two different combinations of antimicrobials: (a) CHX-Cu++, (b) PPi-SDS-F. 2. Determine the effect of subMIC concentrations of CHX-Cu++ and PPi- SDS-F on (a) expression of phenotypically-active glucan-binding lectins of the mutans streptococci, and (b) the ability of these organisms to adhere and colonize glucan-coated surfaces. 3. Delineate the effects of CHX-Cu++ and PPi-SDS-F combinations pulsed (high initial concentration) or dosed (low initial concentration gradually increased) on communities of oral bacteria grown in continuous culture. 4. Determine the effect of CHX-Cu++ and PPi-SDS-F combinations on plaque development and demineralization of enamel sections in an intraoral appliance model. The results from this grant will provide important information on these antimicrobial combinations and their potential anti-caries properties.